ABSTRACT The Sidney Kimmel Comprehensive Cancer Center (SKCCC) Cancer Biology (CB) Program's overall goal is to understand the cellular and molecular alterations that drive human tumorigenesis and to exploit the translational potential of this information for cancer diagnosis, therapy and prevention. The translational mission was accentuated in the current cycle through the addition of Program members with expertise in developing clinical trials, translating findings from the Program. The Program has been part of the CCSG for over 25 years and is composed of 39 SKCCC faculty members representing eight departments of the School of (Medicine, Oncology, Otolaryngology?Head and Neck Surgery, Pathology, Radiation Oncology and Molecular Radiation Sciences, Surgery, Molecular Biology and Genetics, Biophysics and Biophysical Chemistry), one from the Bloomberg School of Public Health (Biochemistry and Molecular Biology) and two from the Whiting School of Engineering (Biomedical Engineering, Mechanical Engineering). Faculty members hold appointments in five different graduate programs in the School of Medicine (Cellular and Molecular Medicine, Human Genetics and Molecular Biology, Biochemistry and Molecular Biology, Pharmacology, and Pathobiology) and one in the Bloomberg School of Public Health (Biochemistry and Molecular Biology). The Program is supported by $21 million in NCI and other peer-reviewed support and has 835 total publications? 228 (27%) are Intra-Programmatic, 327 (38%) are Inter-Programmatic and 317 (38%) were multi-institutional collaborations. Virtually all faculty members are housed in the SKCCC Research Complex Buildings, and there are more than 20 graduate students and over 60 Postdoctoral research fellows in the Program. Under the direction of Stephen Baylin, M.D., and Victor Velculescu, M.D., Ph.D., the specific aims of the CB Program are: Aim 1. To define genetic abnormalities that drive human cancer initiation and progression. Program members will continue to define the basic function of the genes and molecular mechanisms underlying human cancer, particularly those that may be amenable to therapeutic or diagnostic intervention. Aim 2. To define the molecular origins of epigenetic changes that underlie tumor initiation and progression and the signaling events they control, and harness this information to design therapeutic strategies and devise biomarker strategies. Aim 3. To translate basic and preclinical findings to investigator-initiated clinical trials led by CB Program members and members of other Programs throughout the SKCCC. The basic research in the Program has increasing translational significance that will continue to move to clinical testing by highly Inter-Programmatic teams in the areas of molecular marker strategies for cancer risk assessment, diagnosis and prognosis, and new strategies for cancer treatment and prevention. Members contribute significantly to the GI, Head and Neck, and Prostate SPOREs, and the leader of the Head and Neck SPORE is a Program member.